1. Field of the Invention
The present invention relates to microsystems for biological analyses for use in the health sector, the food processing industry and the environmental sector.
It is particularly used to produce biological analyses microsystems intended for in vitro diagnostics in analyses of infectious illnesses such as detecting the HIV virus, mycobacteria etc.
In these fields, where it is important to cut costs in the health system, analysis microsystems are currently needed that have a single usage, that are easy to operate, that use only very small amounts of samples and that are based on principles of direct detection that require neither a detection reagent (marker or other means) nor amplification of a detection signal.
2. Discussion of the Background
Approximately four years ago new types of tests appeared such as multi-affinity tests, tests integrating functions such as gene amplification and separation using electrophoresis. The industrial applications of these new types of tests seem to be widespread even though at present they are mainly used in human genome sequencing.
The success of these new tests is mainly due to the micro-technologies that have been introduced into the biological field. Through being integrated and combined, the micro-technologies have enabled high performance levels to be reached and speeds and sensitivity levels to be increased. Furthermore, micro-technologies have led to new technical solutions such as miniaturization and integration and new economic solutions such as mass production, thus giving the development of biosensors new impetus.
For example, systems capable of directly performing immunochemical tests have recently been launched. These test systems consist of thin layers of a semiconductor material and silica with antibodies covalently bonded to these layers, said antibodies enabling the presence of an antigen to be detected that is capable of reacting with the antibodies by measuring the capacitance of the assembly (see reference 1: Battaillard et al., in "Analytical Chemistry", 60, 1988, pages 2,374 to 2,379). Another microsystem of the same type is described by Schyberg et al. in reference 2: "Sensors and Actuators", B26-27, 1995, pages 457 to 460.
The documents of reference 3: FR-A-598 227 and 4: EP-A-244 326 also describe a method for detecting and/or identifying a biological substance in a liquid sample by means of electrical measurements. According to this method, the sample is brought into contact with a reagent support plate that comprises a specific ligand of the biological substance to be detected. Said plate can be made of a semiconductor material such as silicon and can be coated with an insulating layer of silica. The constituents C and/or R are then measured for the electrical impedance of the system in order to detect whether the biological substance is present in the sample.
All these systems use the recognition reaction between the biological substance to be detected and a specific ligand of the substance to be able to detect said biological substance directly without other reagents or means of detection such as markers, signal amplification reactions, etc. having to be used. This recognition reaction causes an active layer to form that has electrical characteristics, for example a capacitance and an impedance that are different from those in the system without the said layer.
However, the systems that exist at present do not allow for any other measurement other than electrical impedance to be used and they are not suitable for measuring near to or within the active layer.